Microvolume handling systems have attracted a considerable interest in biochemical analysis, combinatorial chemistry and high throughput screening (HTS) applications. The miniaturised format is compatible in size with many interesting issues of bioanalytical work, such as single cell analysis, when material is available only in extremely limited amounts. Furthermore, by decreasing the volume, an enhanced efficiency in terms of a higher rate of mixing and/or chemical reaction can be expected in the sample container, since the effect of diffusion and thermal convection is more pronounced on a smaller scale.
In HTS applications, goals are currently set on screening more than 105 compounds in a single assay. To manage such a tremendous number of samples with reasonable space, cost and time requirements, the miniaturised microtitre plate format has been developed. Based on micromachining of different materials, e.g., by anisotropically etching single crystalline silicon wafers, well-defined picoliter to nanoliter vials are readily fabricated (Jansson et al. (1992) J. Chromatography 626, 310-314; Beyer Hietpas et al. (1995) J. Liq. Chromatography 18, 3557-3576). Biomolecules such as DNA and proteins have been assayed in the microvial format utilising capillary electrophoresis (Jansson et al. supra; Beyer Hietpas et al., supra), bioluminescence (Crofcheck et al. (1997) Anal. Chem. 69, 4768-4772), electrochemical analysis (Clark et al. (1997) Anal. Chem. 69, 259-263; Clark et al. (1998) Anal. Chem. 70, 1119-1125) and mass spectrometry (Jespersen et al. (1994) J. Rapid Comm. in Mass Spectrom. 8, 581-584).
However, the rate of solvent evaporation is particularly pronounced for microvolumes, for instance small droplets, since the surface-to-volume ratio increases when the drop diameter decreases. The most common way for avoiding desiccation is by covering the containers with a material non-permeable for the underlying solvent. However, covers, either liquid or solid, inherently have the potential to introduce interfering compounds, or to alter equilibriums, that can seriously damage sensitive chemical systems. Furthermore, practical problems may arise from small droplets sticking to a solid cover.
An alternative is to diminish the solvent loss by controlling the environment in humidified chambers and by dispensing compensating solvent into the microvials via fine capillaries from above (Roeraade et al. (1996) Analytical Methods and Instrumentation. Special issue μTAS'96 (1996), pp. 34-38). However, this technique can be ineffective over prolonged time periods and is subject to many practical problems associated with the restricted accessibility to the vials through the environmental chamber. Furthermore, since the solvent compensating capillaries block the space in close proximity to the microvials, accessing or detecting the material becomes increasingly more complex as the assay becomes larger.
There is a need for microfluidic devices including a system for handling small volumetric amounts of liquid which avoids the above discussed drawbacks and allows for free access to the contained material, thus facilitating chemical manipulation of the liquid or the gaseous headspace environment and for monitoring of reaction products.
A device having the features of claim 1 and a method having the features of claim 6 fulfill this need.